Management of Men with PSA Recurrence after Radical Local Radiation - - PowerPoint PPT Presentation

Felix Feng, MD

Vice Chair, Department of Radiation Oncology Professor of Radiation Oncology, Urology, and Medicine University of California at San Francisco Chair, GU Cancer Committee, NRG/RTOG

Management of Men with PSA Recurrence after Radical Local Radiation Therapy

Disclosures

§ I have consulted for Astellas, Dendreon, EMD Serono, Ferring, Genentech, Bayer, Clovis, Janssen, Sanofi, and Blue Earth Diagnostics. § I am co-founder of PFS Genomics, a molecular diagnostics company in the breast cancer space. § I am on the Scientific Advisory Board for Nutcracker Therapeutics and SerImmune.

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Overview

§ Over 1.2 million patients are diagnosed with prostate cancer worldwide each year1. § In the United States, over one third of patients with localized prostate cancer are treated with radiation therapy (RT)2. § Depending on the disease characteristics, 15-70% of prostate cancer patients recur after definitive RT. § These figures suggest that over 100,000 men may present with recurrent disease after upfront RT.

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1Bray F et al, CA CANCER J CLIN 2018; 68: 394-424, 2Chen J et al, Prostate 2018; 78(7): 512-520.

How do we define a PSA recurrence after RT?

§ RTOG-ASTRO Phoenix Consensus Definition1: PSA increase by 2 ng/mL or more above the nadir PSA § Many clinicians do not wait for Phoenix criteria to be achieved before evaluating for recurrence. § NCCN Guidelines: “A recurrence evaluation should be considered when PSA has been confirmed to be increasing after radiation even if the increase above nadir is not yet 2 ng/mL, especially in candidates for salvage local therapy who are young and healthy.”

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1Roach M et al, IJROBP 65(4): 965-974.

Management of a PSA recurrence after definitive RT

§ Work-up

– Imaging – Potential biopsy

§ Local Therapy for Local Recurrences § Local Therapy for Regional or Distant Recurrences § Systemic Therapy

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Focus of my talk Focus of subsequent talks at APCCC

What is the significance of a local recurrence after RT?

Zelefsky M et al, J Urology 2019, 201 (1127-1133)

Positive post- treatment biopsies are associated with increased incidence

• f distant metastases

Cumulative Incidence of Distant Metastases as a Function of Post-Treatment Biopsy Status

382 patients with post- treatment biopsies after definitive RT for prostate cancer:

• 30% positive (red)
• 22% w/ significant

treatment effect (green)

• 48% negative (blue)

Management of a PSA recurrence after definitive RT

PSA recurrence after RT

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Candidate for local therapy Not a candidate for local therapy

Who are the best candidates for local therapy?

• Original clinical stage T1-2, NX or N0
• Life expectancy > 10 yrs
• PSA now < 10 ng/mL
• Long interval to recurrence (>3 years)
• Long PSA doubling time (>12 months)
• Organ-Confined at Recurrence (i.e., MRI)

Management of a PSA recurrence after definitive RT

PSA recurrence after RT

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Candidate for local therapy Not a candidate for local therapy Local imaging (prostate MRI and TRUS +/- biopsy) Bone imaging (bone scan and PET/CT* or PET/MR*)

*PET can be PSMA or fluciclovine or C-11 choline PET

Detection of a local recurrence

Kanthabalan A et al, Clinical Oncology 2016, 28: 568-576

Data from 77 patients who underwent Transperineal Prostate Mapping (TPM) with 5 mm sampling as well as MRI-Targeted Biopsies (MRI-TB) with multi-parametric MRI

Cancer Detection Rates: Core-Based Comparison:

Management of a PSA recurrence after definitive RT

PSA recurrence after RT

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Candidate for local therapy Not a candidate for local therapy Local imaging (prostate MRI and TRUS +/- biopsy) Bone imaging (bone scan and PET/CT* or PET/MR*) Bone imaging (bone scan and PET/CT* or PET/MR*)

*PET can be PSMA or fluciclovine or C-11 choline PET

Advanced imaging has changed our ability to detect disease at low PSA levels

Prospective study: PSMA PET imaging performed on 635 patients, including 169 treated with definitive radiation therapy All PET-detected lesions validated with histopathological assessment or a composite endpoint based on imaging and PSA follow-up

Fendler W et al, JAMA Oncology 2019, 5(6): 856-863

Advanced imaging has changed our ability to detect disease at low PSA levels

Retrospective study: Detection rates of

68Ga-PSMA PET in

276 patients treated with definitive radiation therapy Patterns of recurrence in this cohort:

Raveenthiran S et al, Prostate Cancer and Prostatic Diseases, 2019, 22: 385-390

15-30% have isolated local failures

Not biopsy proven

Using PSMA PET to determine patterns of disease recurrence following primary radiotherapy

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Raveenthiran S et al, Prostate Cancer and Prostatic Diseases, 2019, 22: 385-390

PSMA PET detects more lesions than Axumin PET

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Calais J et al, Lancet Oncology 2019

Management of a PSA recurrence after definitive RT

PSA recurrence after RT

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Candidate for local therapy Not a candidate for local therapy Local imaging (prostate MRI and TRUS +/- biopsy) Bone imaging (bone scan and PET/CT* or PET/MR*) Bone imaging (bone scan and PET/CT* or PET/MR*)

*PET can be PSMA or fluciclovine or C-11 choline PET

No mets & TRUS biopsy + Mets present

• r TRUS

biopsy negative Observation

• r ADT +/-

MDT** Local therapy

• ptions:

Brachytherapy Radical prostatectomy +/- lymph node dissection High-intensity focused ultrasound Cryotherapy SBRT?

**MDT = Metastases-directed therapy

Table&1&=&Guidelines&for&…&second4line&therapy&after&txt&with&curative&intent BCR&after&RT

• Treat&highly&selected&pts&with&localized&PC&&&histologically&proven&local&

recurrence&with&salvage&RP

• Due&to&the&increased&rate&of&side&effects,&perform&salvage&RP&in&

experienced&centres

• Offer&or&discuss&HiFu,&Cryo and&salvage&brachy&with&pts&without&mets …&

inform&pts&about&the&experiental&nature&of&these&approaches LE&GR 3 B 3&&&&&A 3&&&&B Local&salvage&treatment

European Guidelines

Approaches for treatment of a local recurrence

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Almost all studies of salvage therapies for post-RT local recurrences are retrospective 5 year FFS rates are approximately the same for all modalities (52-56%)

Parekh A et al, Semin Radiat Oncol 23:222-234

RTOG 0526: A Prospective Phase 2 Trial of Transperineal Ultrasound-Guided Brachytherapy for Locally Recurrent Prostate Cancer After External Beam Radiation Therapy

§ 92 patients received salvage LDR brachytherapy from 2007-2014 § Prescribed minimum target dose: I-125 (140 Gy), Pd-103 (120 Gy) § Primary endpoint (late GI/GU adverse events): 13.8% of patients had late treatment-related GI/GU AE’s (hypothesis was that <10% of patients would have these AE’s, but >20% was considered unacceptable) § MVA logistic regression: No pre treatment characteristics predicted

• ccurrence of late treatment-related GI/GU AE’s

Crook J et al, IJROBP 2019, 103(2): 335-343

Conclusions

§ There is a significant subset of prostate cancer patients with PSA recurrences after definitive RT. § Positive post-treatment biopsies are associated with metastatic progression. § Advanced imaging approaches allow detection of recurrences at PSA levels lower than the nadir + 2 (phoenix) definition. § Treatment approaches for biopsy-proven local recurrences (in the absence of metastases) include salvage brachytherapy, RP, HiFU, and cryotherapy.